Process for preparing 3-chloro-5-nitrotoluene

ABSTRACT

A preparation process of 3-chloro-5-nitrotoluene is provided in mild conditions. It is a process for preparing 3-chloro-5-nitrotoluene, which comprises reacting 2-methyl-4-nitroaniline with a chlorinating agent such as 5-butyl hypochlorite in a neutral condition to obtain 2-chloro-4-nitro-6-methylaniline and deaminating the 2-chloro-4-nitro-6-methylaniline to obtain 3-chloro-5-nitrotoluene.

FIELD OF ARTS OF THE INVENTION

[0001] The invention relates to a process for preparing3-chloro-5-nitrotoluene and a process for preparing3-chloro-5-methylphenylisocyanate.

PRIOR ARTS

[0002] JP-A 8-231489 and J. Med. Chem. 43, 4726-4737 (2000) show aprocess for preparing an isocyanate reacting with a polysaccharide andhaving a high separation power.

[0003] JP-A 8-231489 discloses a production process using potassiumchloride in hydrochloric acid. The reference production process needsany improvement because a strong acid is used and a salt formed byneutralization of the product mixture has to be treated.

[0004] J. Med. Chem. discloses a reaction of 4-methyl-2-nitroanilinewith N-chlorosuccinic imide. In the reference reaction, purificationwith column chromatography is necessary to separate the intended productfrom a side-produced succinicimide. It is not suitable to a large-scaledproduction.

SUMMARY OF THE INVENTION

[0005] The invention relates to a process for preparing3-chloro-5-nitrotoluene in mild conditions, without any strong acid andany strong base, to obtain an isocyanate precursor and then a processfor preparing 3-chloro-5-methylphenylisocyanate, which is useful toproduce an optical separation agent.

[0006] The invention provides, as means to solve the above shownproblems, a process for preparing 3-chloro-5-nitrotoluene, whichcomprises reacting 2-methyl-4-nitroaniline with a chlorinating agent ina neutral condition to obtain 2-chloro-4-nitro-6-methylaniline anddeaminating the 2-chloro-4-nitro-6-methylaniline to obtain3-chloro-5-nitrotoluene.

[0007] The invention provides, as means to solve another problem, aprocess for preparing 3-chloro-5-methylphenylisocyanate, which comprisesreducing 3-chloro-5-nitrotoluene obtained by the above shown process andreacting the resulting product with triphosgene.

DETAILED EXPLANATION OF THE INVENTION

[0008] The preparation of 3-chloro-5-nitrotoluene will be explained inline with the following reaction formula 1.

[0009] 2-methyl-4-nitroaniline, (1) of the reaction formula 1, is firstreacted with a chlorinating agent in a neutral condition to obtain2-chloro-4-nitro-6-methylaniline, (2) of the reaction formula 1.

[0010] The reaction is preferably carried out in a solvent containingneither acid nor base at room temperature. The solvent is notparticularly limited, as far as it is a solvent for both2-methyl-4-nitroaniline and the chlorinating agent including, forexample, toluene, benzene, acetic acid etc.

[0011] The chlorinating agent includes, for example,t-butylhypochlorite, N-chlorosuccinic imide etc.

[0012] The reaction product of 2-chloro-4-nitro-6-methylaniline isisolated by filtering etc. in advance to the subsequent reaction step.It may be washed or dried if necessary.

[0013] Then 3-chloro-5-nitrotoluene, (3) of the reaction formula 1, isobtained from 2-chloro-4-nitro-6-methylaniline by deamination.

[0014] The deamination reaction for 2-chloro-4-nitro-6-methylaniline mayproceed in a solvent such as ethanol or methanol. The reactiontemperature is preferably controlled into plural steps in the followingmanner.

[0015] In the first step, the reaction mixture is adjusted between roomtemperature and 0° C., preferably 5 and 10° C., and then sodium nitriteis added thereto, preferably in the form of an aqueous solution ofsodium nitrite of 1 to 2 mole equivalents.

[0016] In the second step, the reaction mixture is allowed to stand,preferably stirred, at room temperature, it is observed that thetemperature elevates up to about 45° C. by way of the reaction heat andthen decreases down to lower than 40%, then the reaction mixture isstirred at a temperature of 40 to 50° C. until no foaming.

[0017] In the third step, the reaction mixture is cooled to roomtemperature and the reaction product is isolated by filtering or thelike.

[0018] The preparation of 3-chloro-5-methylphenylisocyanate will bebelow explained in line with the following reaction formula 2.

[0019] 3-chloro-5-nitrotoluene, (3) of the reaction formula 2, is firstdissolved in a solvent such as ethanol and the solution is reacted,while cooled, with a reducing agent (a hydrogenating agent) such as tinchloride or Raney nickel to obtain 3-chloro-5-methylaniline, (4) ofreaction formula 2.

[0020] Triphosgene is dissolved in a solvent such as toluene and3-chloro-5-methylaniline and a toluene solution of triethylamine areadded thereto at room temperature for reaction to obtain3-chloro-5-methylphenylisocyanate, (5) of reaction formula 2.

[0021] 3-chloro-5-nitrotoluene, obtained by the preparation of theinvention, is useful as a precursor to3-chloro-5-methylphenylisocyanate. 3-chloro-5-methylphenylisocyanate isuseful to prepare conventional polysaccharides used as opticalseparating agents.

[0022] The process of the invention is carried out in mild conditionsand suitable to a large scaled production.

EXAMPLE

[0023] The invention will be below explained by reference to examples.The invention, however, is not limited by the examples.

Example 1 Preparation of 3-chloro-5-nitrotoluene

[0024] {circle over (1)} Preparation of 2-chloro-4-nitro-6-methylaniline

[0025] 2-methyl-4-nitroaniline (56.0 g, 0.368 mol) was dispersed intoluene (430 ml) in a 1 liter four-neck flask. Tirtiary butylhypochloride (46.0 g, 0.423 mol) was added dropwise thereto, whilecooled in iced water and stirred. The mixture was stirred at roomtemperature for 3 hours. The solid was filtered and washed three timeswith 200 ml of a 50% aqueous ethanol three times. It was then dried at40 at a reduced pressure to obtain 55.33 g of a yellow solid (productionyield 80%). The yellow solid was used at the subsequent step withoutpurification.

[0026]¹H-NMR, 500 MHz, in CDCl₃ (δ)

[0027] 8.12 (d, J=2.2 Hz, 1H)

[0028] 7.92 (d, J=2.2 Hz, 1H)

[0029] 4.73 (bs, 2H)

[0030] 2.27 (s, 3H)

[0031] {circle over (2)} Preparation of 3-chloro-5-nitrotoluene

[0032] 2-chloro-4-nitro-6-methylaniline (55.0 g, 0.295 mol) and ethanol(500 ml) were mixed in a 2 litter four-neck flask. A conc. Sulfuric acid(120 ml) was added dropwise to the reaction mixture at a temperaturebeing lower than room temperature. The reaction mixture was maintainedat a temperature of 5 to 10° C. and an aqueous solution of sodiumnitrite (26.44 g, 0.381 mol/40 ml) was added dropwise thereto over aperiod of 40 minutes.

[0033] The reaction mixture was then stirred at room temperature. It wasobserved that the temperature elevated up to 45° C. by way of thereaction heat and then decreases down to lower than 40° C. and then thereaction mixture was stirred at a temperature of 40 to 45° C. until nofoaming.

[0034] The product mixture was cooled to room temperature and pouredinto 2500 ml of iced water to obtain precipitates. They were filteredand dried at a reduced pressure to obtain 45.95 g of a yellow solid(production yield 90%).

[0035]¹H-NMR, 500 MHz, in CDCl₃ (δ)

[0036] 8.03 (bs, 1H)

[0037] 7.94 (bs, 1H)

[0038] 7.50 (bs, 1H)

[0039] 2.46 (s, 3H)

Example 2 Preparation of 3-chloro-5-methylphenylisocyanate

[0040] {circle over (1)} Preparation of 3-chloro-5-methylaniline

[0041] 3-chloro-5-nitrotoluene (45 g, 0.241 mol) and ethanol (500 ml)were mixed in a 2 litter four-neck flask. The mixture was cooled toabout 4° C. A solution of tin chloride monohydrate (217.67 g, 0.965 mol)in 200 ml of ethanol was added dropwise to the mixture over 2 hours,while the reaction mixture was maintained at 10° C. or lower.

[0042] Then the reaction product mixture was stirred at room temperaturefor 2 hours and poured into 2500 ml of iced water. It was neutralizedwith sodium hydroxide and filtered with a nutsche filled with sellaite.The residue was washed with ethyl acetate. The intended product wasobtained with ethyl acetate from the filtrate liquid.

[0043] Then the extract liquid and the washing liquid were jointed. Themixture was washed with water and then a saturated salt water and driedwith magnesium sulfate. Concentrated, it was treated by distillation ata reduced pressure to obtain 28.0 g of a yellow liquid (production yield80%).

[0044] B.p.: 85-92° C./0.4 kPa or lower (3 Torr or lower)

[0045]¹H-NMR, 500 MHz, in CDCl₃ (δ)

[0046] 6.56 (bs, 1H)

[0047] 6.48 (dd, JI, J2=1.3 Hz, 1H)

[0048] 6.36 (bs, 1H)

[0049] 3.64 (bs, 2H)

[0050] 2.22 (s, 3H)

[0051] {circle over (2)} Preparation of3-chloro-5-methylphenylisocyanate

[0052] Triphosgene (17.01 g, 0.0573 mol) was dissolved in 200 ml oftolunen in a 1 liter flask. 150 ml of a toluene solution of3-chloro-5-methylaniline (21.9 g, 0.155 mol) and triethylamine (36.0 ml)was added dropwise thereto over 30 minutes at room temperature.

[0053] The reaction mixture was then stirred at 70° C. for 2 hours andcooled to room temperature. The obtained precipitates of hydrochloricacid salt of triethylamine were filtered out and the filtrate liquid wasconcentrated and treated with distillation at a reduced pressure toobtain 16.87 g of a colorless liquid (production yield 65%).

[0054] B.p.: 72-74° C./0.53-0.66 kPa (4-5 torr)

[0055]¹H-NMR, 500 MHz, in CDCl₃ (δ)

[0056] 7.00 (bs, 1H)

[0057] 6.90 (bs, 1H)

[0058] 6.80 (bs, 1H)

[0059] 2.31 (s, 3H)

1. A process for preparing 3-chloro-5-nitrotoluene, which comprisesreacting 2-methyl-4-nitroaniline with a chlorinating agent in a neutralcondition to obtain 2-chloro-4-nitro-6-methylaniline and deaminating the2-chloro-4-nitro-6-methylaniline to obtain 3-chloro-5-nitrotoluene. 2.The process as claimed in claim 1, in which the reaction of2-methyl-4-nitroaniline with a chlorinating agent is carried out in asolvent containing neither acid nor base.
 3. The process as claimed inclaim 1 or 2, in which the chlorinating agent is t-butylhypochlorite. 4.The process as claimed in any of claims 1 to 3, in which the deaminationis carried out by adding sodium nitrite to the reactant mixture adjustedbetween room temperature and 0° C., allowing the reaction mixture tostand at an elevated temperature and then decreasing the temperature andkeeping it at a temperature of 40 to 50° C.
 5. A process for preparing3-chloro-5-methylphenylisocyanate, which comprises reducing3-chloro-5-nitrotoluene obtained by any process as defined in claims 1to 4 and reacting the resulting product with triphosgene.